We present data supporting the hypothesis that the lysosomal-autophagy pathway is involved in the degradation of intracellular triacylglycerols in the liver. In primary hepatocytes cultivated in the absence of exogenous fatty acids (FFA), both inhibition of autophagy flux (asparagine) or lysosomal activity (chloroquine) decreased secretion of VLDL (very low density lipoproteins) and formation of FFA oxidative products while the stimulation of autophagy by rapamycine increased some of these parameters. Effect of rapamycine was completely abolished by inactivation of lysosomes. Similarly, when autophagic activity was influenced by cultivating the hepatocytes in "starving" (amino-acid poor medium) or "fed" (serum-supplemented medium) conditions, VLDL secretion and FFA oxidation mirrored the changes in autophagy being higher in starvation and lower in fed state. Autophagy inhibition as well as lysosomal inactivation depressed FFA and DAG (diacylglycerol) formation in liver slices in vitro. In vivo, intensity of lysosomal lipid degradation depends on the formation of autophagolysosomes, i.e. structures bringing the substrate for degradation and lysosomal enzymes into contact. We demonstrated that lysosomal lipase (LAL) activity in liver autophagolysosomal fraction was up-regulated in fasting and down-regulated in fed state together with the increased translocation of LAL and LAMP2 proteins from lysosomal pool to this fraction. Changes in autophagy intensity (LC3-II/LC3-I ratio) followed a similar pattern.

• MeSH
• asparagin farmakologie   MeSH
• autofagie účinky léků   MeSH
• chlorochin farmakologie   MeSH
• diglyceridy metabolismus   MeSH
• hepatocyty metabolismus   patologie   účinky léků   MeSH
• játra metabolismus   patologie   účinky léků   MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• kyseliny mastné neesterifikované metabolismus   MeSH
• lipolýza MeSH
• lipoproteiny VLDL metabolismus   MeSH
• lyzozomy metabolismus   patologie   účinky léků   MeSH
• membránový protein 2 asociovaný s lyzozomy metabolismus   MeSH
• oxidace-redukce MeSH
• potkani Wistar MeSH
• proteiny asociované s mikrotubuly metabolismus   MeSH
• sirolimus farmakologie   MeSH
• sterolesterasa metabolismus   MeSH
• triglyceridy metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH